Peptide argininal (aldehyde group C-terminal) compounds will be synthesized and their inhibition constants determined against a select group of plasma enzymes that play a role in thrombosis and fibrinolysis. Aldehyde synthesis will be carried out by a Pfitzner-Moffatt oxidation of the amino acid alcohol or by direct reduction of the amino acid ester with dibutyl aluminum hydride. Inhibition constants will be obtained against the appropriate substrates by standard techniques. Variation in the peptide argininal sequence within the small peptide aldehydes will be studied to determine the selectivity and specificity of inhibition. The aldehyde peptides when associated with the protease may mimic features of the reaction transition-state, and it is predicted that these transition-state analogs may associate with affinity constants 10 to the second power to 10 to the fourth power times higher than their natural substrates and with high specificity. The peptide aldehydes will be attached to sepharose resin to ascertain the usefulness as a general procedure for plasma protease purification by affinity chromatography. The availability of high affinity inhibitors with selective ability to associate with a single thrombolytic enzyme within a group of plasma enzymes will also be important for the study of hemostasis and related process; and in the development of anti-thrombolytic drugs with high specificity. The methodology makes use of a particular enzyme's high selective affinity to its transition-state. The research will serve as a model for the general development of selective protease inhibitors in which an acid product of a protease's action is isolated, chemically transformed to a N-acyl-aldehyde derivative, and used in biological and purification studies of the parent protease.